What are the dangers of using Unisom (doxylamine) and hydroxyzine?

Dangers of Combining Unisom (Doxylamine) and Hydroxyzine

The combination of doxylamine (Unisom) and hydroxyzine presents significant dangers due to their additive central nervous system depressant effects, which can lead to excessive sedation, cognitive impairment, and potentially life-threatening cardiac complications including QT prolongation and Torsade de Pointes. 1

Primary Risks of This Combination

Additive CNS Depression

• Both medications are potent sedatives that act on the central nervous system
• When combined, they produce enhanced drowsiness, sedation, and cognitive impairment 2, 1
• This combination significantly increases risk of:
  • Impaired coordination and balance
  • Decreased reaction time
  • Increased risk of falls, especially in elderly patients
  • Impaired driving ability and operation of machinery 2

Cardiovascular Risks

• Hydroxyzine carries FDA warnings for QT prolongation and Torsade de Pointes (potentially fatal cardiac arrhythmia) 1
• Risk factors that increase cardiac dangers:
  • Pre-existing heart disease
  • Electrolyte imbalances
  • Concomitant use of other medications that prolong QT interval
  • Recent myocardial infarction
  • Uncompensated heart failure
  • Bradyarrhythmias 1

Potential for Dependence and Abuse

• Doxylamine has documented potential for abuse and addiction 3
• Case reports show escalation from therapeutic doses (25mg) to much higher doses (125mg/day) 3
• Hydroxyzine may also contribute to dependence when used chronically

Special Population Considerations

Elderly Patients

• Significantly higher risk of adverse effects in elderly populations
• Increased sensitivity to psychomotor impairment
• Higher risk of falls and confusion
• Dosing should start at lowest possible levels (if used at all) 2

Patients with Hepatic or Renal Impairment

• Both medications may have prolonged effects in patients with impaired metabolism
• Hydroxyzine requires dose reduction (50%) in moderate renal impairment
• Hydroxyzine should be avoided entirely in severe renal impairment 2

Drug Interaction Mechanisms

Pharmacodynamic Interactions

• Both medications have anticholinergic properties that can cause:
  • Dry mouth
  • Blurred vision
  • Urinary retention
  • Constipation
• Additive cognitive impairment - morning doses of hydroxyzine show greater cognitive impairment than evening doses 4

Contraindicated Combinations

• This combination should not be used with:
  • Alcohol or other CNS depressants
  • Opioids
  • Benzodiazepines
  • Barbiturates
  • Monoamine oxidase inhibitors 1, 5
  • Other medications that prolong QT interval (Class 1A or Class III antiarrhythmics, certain antipsychotics, antidepressants, and antibiotics) 1

Safer Alternatives

• For insomnia: Short-acting benzodiazepine receptor agonists or ramelteon (for patients with substance use concerns) 2
• For anxiety: SSRIs, SNRIs, or buspirone
• For allergic conditions: Second-generation antihistamines with less CNS penetration

Bottom Line

The combination of doxylamine and hydroxyzine should be avoided due to significant risks of excessive sedation, cognitive impairment, and potential cardiac complications. If either medication is necessary, they should not be used concurrently, and healthcare providers should consider safer alternatives based on the patient's specific condition.